GENE THERAPY FOR CYSTIC FIBROSIS USING CATIONIC LIPOSOME MEDIATED GENE TRANSFER

将正常人CFTR转移至人CF上皮细胞，呼吸道 CF小鼠或人鼻气道的上皮（使用腺病毒载体） 可能导致CFTR介导的氯离子转运的重建。 基因 这些模型中CF生物电缺陷的转移介导校正 系统表明研究基于基因转移的 在疾病中的协议。在本协议中，我们评估了阳离子 正常CFTR递送至鼻呼吸道的基于脂质体的机制 CF患者的上皮细胞。 患者接受一次性给药， 单剂量的含有DMRIE/DOPE（脂质）的脂质/DNA制剂和 编码全长CFTR的质粒DNA。到目前为止，我们已经研究了三个 病人和结果是令人鼓舞的。成功的基因转移 在三名患者中的两名中观察到，没有毒性或 在鼻气道、肺或其他器官中观察到副作用 系统. 由于这些令人鼓舞的发现，我们打算研究六个 在不久的将来，更多的病人。

Transfer of normal human CFTR to human CF epithelial cells, respiratory epithelium of CF mice, or human nasal airways (using adenoviral vectors) may lead to re-establishment of CFTR mediated chloride transport. Gene transfer mediated correction of the CF bioelectric defect in these model systems indicate the importance of investigating gene transfer-based protocols in the disease. In the present protocol, we evaluate a cationic liposome-based mechanism of delivery of normal CFTR to nasal respiratory epithelia of CF patients. Patients undergo one-time administration of a single dose of a lipid/DNA formulation containing DMRIE/DOPE (lipid) and plasmid DNA encoding the full length CFTR. To date, we have studied three patients and the results have been encouraging. Successful gene transfer was observed in two of three patients, and no evidence of toxicities or side effects were observed in the nasal airways, lung, or other organ systems. Because of these encouraging findings, we intend to study six additional patients in the near future.